1. Field of the Invention
The present invention provides the RSP-1 and RSP-2 proteins which are involved in the cytoadhesion of P. falciparum during ring-stage infection of erythrocytes, antibodies which bind to the proteins, methods of screening for a P. falciparum infection, methods of determining the infective stage of P. falciparum and vaccines for protecting individuals from Plasmodium sp. infections.
2. Description of the Background
A common pathological characteristic in P. falciparum infection is the cytoadbesion of mature-stage infected erythrocytes (IE) to host endothelium and syncytiotrophoblasts. Massive accumulation of IE in the brain microvascular or placenta is strongly correlated with severe form of malaria1. Extensive binding of IE to placental CSA is associated with physiopathology during pregnancy2,3. The adhesive phenotype of IE correlates with the appearance of POEMP1 at the erythrocyte surface (approx. 16 hours after merozoite invasion) and therefore only early blood-stage (ring-stage) IE are seen in the peripheral blood. Here we describe results that challenge the existing view of blood-stage IE biology. We demonstrate the specific adhesion of IE, during the early ring-stage, to endothelial cell lines from brain and lung and to placental syncytiotrophoblasts. Later in the blood-stage development of these IE, trophozolites switch to an exclusively chondroitin-sulphate A (CSA) cytoadhesion phenotype. Therefore, adhesion to an individual endothelial cell or syncytiotrophoblast may occur throughout the blood stage cycle, suggesting that there are non-circulating (cryptic) parasite subpopulations in malaria patients. We detected two novel parasite proteins on the surface of ring-stage EI. These proteins disappear shortly after the start of PfEMP1-mediated adhesion. These data have important implications for epidemiological studies, parasite tissue tropism and malarial disease outcome.